Do Neurons Require Astrocyte-Derived Lactate for Energy? Astrocyte-Neuron Metabolic Coupling is Mediated by Calcium Waves and Sodium Current in the Tripartite Synapse: Therapeutic Implications for Some Brain Diseases Involving Metabolic Dysregulation
Author(s): Menizibeya O Welcome
The most widely accepted model of brain glucose metabolism is the astrocyte-neuron lactate shuttle (ANLS) hypothesis. However, in recent times, ANLS has met serious criticism as the model could not account for new data indicating that neurons may not require astrocyte-derived lactate for energy. Proponents of the hypothesis still believe that ANLS describes key aspects of brain glucose metabolism and holds therapeutic promise for some brain diseases including mental and substance disorders. Indeed dysfunctions of metabolic machinery of both astrocytes and neurons have been implicated in diseases involving cerebral glucose metabolic dysregulation, suggesting that these cells play a synergic role in glucose metabolism. Unfortunately, however, the cellular and molecular nexus linking astrocyte-to-neuron metabolism has not been fully unraveled. In this review, data on opposing views of brain glucose metabolism are reconciled. It is suggested that metabolic machinery of astrocytes and neurons is coupled to each other via calcium waves and sodium current, mediated by the tripartite synapse, an anatomo-physiologic spatiotemporal integration site, formed by the physical proximity of the membranes of presynaptic neuron, postsynaptic neuron, and astrocyte. The therapeutic implication of this view of astrocyteneuron glucose metabolism is also discussed.